Confocal microscope

对运动的控制、对环境信息的反应、记忆的形成……我们所有的活动都依赖于神经系统的功能。神经系统在进化过程中获得的非凡能力和支持这些活动的能力依赖于神经系统中单个细胞的精确结构和它们之间形成功能回路的相互作用。个体神经元的结构和神经元之间的连接是在个体发育过程中形成的，它们在动物成年期会发生可塑性变化，在动物老年期会被破坏或解体。我们研究神经元在发育过程中如何阐述其复杂和神经元类型特定的形态。这些是具有复杂空间和时间维度的动态过程，只能在体内解决。为了阐明它们的细胞和分子机制，我们利用黑腹果蝇发育时间短、幼虫表皮透明和易于基因操作的优势。为了可视化细胞动力学方面，我在工业大学新成立的教授职位需要一台共聚焦显微镜。请求的显微镜将支持我们的工作，记录体内神经元在几秒钟内发生的形态变化，以及分子参与者在这些过程中的动态亚细胞分布。为了实现细胞动力学的长期体内成像，该装置必须结合高空间和时间分辨率，并具有高灵敏度的检测，以最大限度地减少动物持续的照明。除了分析发育中的动物的单个细胞外，我们还研究神经元如何相互作用以形成功能回路。这些相互作用的三维结构还需要通过压电控制z步进允许的快速体积扫描。为了研究神经回路中神经元之间的功能连接，它们的可塑性和退化条件下的潜在退化，我们进一步阐明了神经回路中突触的分子组织。考虑到突触的大小和其中单个分子组分的相对距离，所要求的设置将提供同时具有多个检测通道的超分辨率成像。这台显微镜将成为我在工业大学实验室里几乎所有项目的关键仪器。因此，它对提案中描述的广泛应用的适应性，以及易于维护和可达支持的存在将是至关重要的。

The control of movement, the response to environmental information, the formation of memories… all of our activities depend on the function of the nervous system. The extraordinary capacities that the nervous system has acquired during evolution and that support these actions rely on the precise architecture of the individual cells in the nervous system and of their interactions to form functional circuits. The structure of individual neurons and the connections among neurons into ensembles emerge during the individual’s development, they can undergo plastic changes into the adult life of the animal and can be damaged or disassembled in the aged animal. We study how neurons elaborate their complex and neuron-type specific morphologies during development. These are dynamic processes with complex spatial and temporal dimensions that can only be tackled in vivo. To elucidate their cellular and molecular mechanisms, we thus utilize the fruit fly Drosophila melanogaster, taking advantage of its short developmental time, the transparency of the larval cuticle- and the easy of genetic manipulation. To visualize the cellular dynamics aspects, we request a confocal microscope for my newly established Professorship at the RWTH. The requested microscope will support our work recording the morphological changes of neurons happening in vivo within seconds, as well as the dynamic subcellular distribution of molecular players during these processes. To allow long-term in vivo imaging of cellular dynamics, it is essential that the setup combines high spatial and temporal resolution, with highly sensitive detection to minimize the illumination sustained by the animal. In addition to the analysis of individual cells in the developing animal, we investigate how neurons interact with each other to form functional circuits. The three-dimensional architecture of these interactions requires in addition rapid volumetric scans allowed by a piezo-controlled z stepping. To investigate the functional connections among neurons in circuits, their plasticity and potential degradation in degenerative conditions, we furthermore elucidate the molecular organization of synapses within circuits. Given the size of synapses and the relative distance of individual molecular components within them, the setup requested will afford superresolution imaging with multiple detection channels simultaneously. This microscope will be a key instrument for almost every project in my lab at the RWTH. Therefore, its adaptability to the broad spectrum of applications described in the proposal, as well as its easy maintenance and the presence of reachable support will be of vital importance.